Objective: To identify factors associated with high health care charges in patients diagnosed with diabetic neuropathy (DN). Methods: Data were extracted from a large, commercial health plan database between July 2004 and June 2006. Patients aged 18-64 were selected if they had a DN diagnosis (ICD9: 357.2x; 250.6x) between July 2004 and June 2005 (Year 1) and were continuously enrolled over the study period. High (low) charges groups were constructed for patients in the top and bottom decile of annual charges. Comorbidities in Year 1 were identified, and total charges in Year 2 (July 2005-June 2006) were examined. Logistic regression was used to identify factors associated with high charges. The factors considered were age, gender, type of health plan, and other comorbidities. Results: A total of 8655 DN patients (mean age 51 years, 46% female) were included in the study. Compared to the low charges group, patients in the high charges group had significantly more unique number of co-morbid medical conditions (16 vs. 10) and higher charges ($231,898 vs. $20,213) (both p<0.001). The high charges group contributed 56% of the total charges of all DN patients. Factors significantly (p<0.001) contributing to high charges included dialysis status (OR =19.2),metastatic cancer and acute leukemia (OR=3.4), end-stage liver disease (OR=2.8), renal failure (OR=2.8), kidney transplant status (OR=2.8), severe hematological disorders (OR=2.4), decubitus ulcer of skin (OR=1.9), congestive heart failure (OR=1.9), pancreatic disease (OR=1.7), and major depressive/bipolar/paranoid (OR=1.7), peripheral vascular disease (OR=1.6), and type 1 diabetes (OR=1.4). Age, gender, and type of insurance were not significantly related to high charges. Conclusion: The most expensive DN patients spent over 50% of the total charges. The comorbidities of DN patients incurred significant treatment charges. Managing comorbidities is important for treating patients with DN.